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Chi Zhang, Wan-Qing Yu, Akina Hoshino, Thomas A Reh, Rachel O Wong; Topographic distributions and maturation of starburst amacrine cells in the fetal human retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1782.
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© ARVO (1962-2015); The Authors (2016-present)
In the retina of several species, choline acetyltransferase (ChAT) is exclusively expressed in two populations of amacrine cells, the ON and OFF starburst amacrine cells (SACs), which form separate, non-random, cell mosaics. The development of SACs has been well characterized in many species, whereas it remains unexplored for the human retina. Here, we examined the emergence and distribution of SACs in the fetal human retina.
Early- and mid-gestation (fetal weeks (Fwk) 10, 13, 14, 16, 17, 19 and 20) human retinal wholemounts were fixed, and immunostained for ChAT to label SACs. In each retina, ChAT immunopositive cells in 78-180 regions of interest (775 x 775 μm2 each), 0 to 12 mm from the fovea, were imaged and reconstructed using confocal microscopy. The putative fovea was identified as a region in temporal retina with the highest L/M cone density. Cell density was measured separately for ON and OFF SACs, and their respective distributions were compared across ages and eccentricities. Nearest neighbor distances and regularity indices of the cell mosaics were calculated for each population across ages.
ChAT immunoreactivity was first observed throughout the entire retina at Fwk13. Unlike the adult human retina, ON SAC density had not peaked in the putative fovea at the fetal ages studied. In contrast, OFF SAC density peaked at the fovea by Fwk14. Two separate ChAT bands were identified in the inner plexiform layer of the foveal region by Fwk14. Separate ON and OFF ChAT bands were observed in far peripheral retina at Fwk16. The distributions of both ON and OFF SACs were already not random at the earliest age when these two populations could be distinguished (Fwk14). At the ages examined, SAC mosaics showed greater regularity in the fovea compared to the peripheral retina.
Our results indicate that human SACs begin to express ChAT between Fwk 10-13, followed shortly by the emergence of the characteristic lamination of the ON and OFF SAC processes. Maturation of SACs and their distributions proceed most rapidly in the fovea. Centroperipheral gradients in cell density appears to emerge earlier for OFF SACs compared to ON SACs.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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